The process of manufacturing dinitroanilines produces by-products of N-nitroso compounds. The quantity of N-nitroso compounds created varies with the process used as well as the herbicide produced. For instance, Trifluralin production usually results in less than 1 weight percent of N-nitroso compounds. Conventional manufacture of Pendimethalin, on the other hand, creates between 10% and 30% by weight of N-nitroso compounds, particularly N-nitroso-pendimethalin. This nitrosamine contaminant must be reduced to very low levels, i.e., less than 1 part per million by weight (ppm) for some herbicides, before the product can be marketed. Allowable levels for nitrosamine contamination varies from 0.5 ppm for N-nitrosodipropylamine in Trifluralin to 135 ppm for N-nitrosopendimethalin in Pendimethalin.
N-nitroso compounds, particularly alkyl nitrosamines, have been identified as carcinogens for a wide range of mammalian species. Several classes of herbicides are known to contain nitrosamine impurities. For example, substituted dinitroaniline derivatives and dimethylamine salts of phenoxyalkanoic acid are major herbicides affected by this problem. Because of the carcinogenic problem, the Environmental Protection Agency in the U.S.A. has limited the allowable concentration to be 135 ppm for N-nitroso-pendimethalin and even lower for nitrosamines in other pesticides. This, of course, has put a great burden upon producers to find ways of avoiding or eliminating such trace impurities in their products.
For a number of years now, pesticide manufacturers have been trying to reduce as much as possible the nitrosamine impurities in their products. Many processes have been developed for the herbicide Trifluralin. For Trifluralin, the parent dinitroaniline is tertiary at the amino substituent, thereby retarding the formation of N-nitroso-trifluralin during production. This resulted in far less N-nitroso compounds being formed than are formed for other related herbicides where the amino substituent is secondary. Crude Trifluralin contains from between 15 to 300 ppm nitrosamine. The nitrosamine impurity in this case is primarily that of the free amine used in the amination process, i.e., N-nitroso-di-propylamine. This compound has a considerably lower molecular weight than the herbicide, allowing removal by simple steam distillation.
The N-nitroso derivative of the herbicide itself is, however, formed during the manufacture of other dinitroaniline compounds. In particular, the manufacture of Pendimethalin generally results in crude product with a N-nitroso-pendimethalin content in excess of 10% by weight. This material is advantageously removed to a level below 1 ppm.
In the industry there currently exist three general approaches for reducing nitrosamine content. One method is to eliminate or deactivate the nitrosating agent before it can react with any amine. Another method is to convert nitrosamines to harmless products. The third method is to physically separate and destroy nitrosamines.
The first approach was taken by U.S. Pat. No. 4,120,905, which discloses the removal of nitrosating agents from 4-chloro-3,5-dinitro benzo-tri fluoride in the presence of a gas and a base. Similarly, German Offenlegungsschrift No. 2,926,946 discloses purification of the dinitro benzene intermediate from nitrosating agents by crystallization. U.S. Pat. No. 4,331,468 describes a method of prevention of nitrosamine formation by the addition of monoalkanolamine retarding agent. U.S. Pat. No. 5,196,585 describes a process of reducing chloroaromatic and other impurities and stabilizing the compound against nitrosamine formation. The process utilizes an aqueous solution of sulfite. Similarly, U.S. Pat. No. 4,440,962 describes a method of removing nitrosating agents from a precursor to Trifluralin with an aqueous solution of a bisulfite. U.S. Pat. No. 4,501,608 describes a method of stabilizing dinitroanilines against nitrosamine formation by incorporating an addition compound of bisulfite with an aldehyde or ketone.
Unfortunately, these processes can not retard the formation of N-nitroso-pendimethalin in the range of ten or more percent by weight during the manufacture of Pendimethalin.
The second method for overcoming the nitrosamine problem is to decompose the already formed nitrosamines into harmless products. There are many processes in the literature to achieve this goal. U.S. Pat. No. 4,226,789 describes a method of removing nitrosamines from a herbicide by contacting the herbicide with either hydrochloric acid or gaseous hydrogen chloride. This process requires substantial quantities of HCl with concomitant additional work up of neutralization, washing and drying. In addition, it has been found that unless long reaction times and large excesses of HCl are used to remove NOCl, a byproduct, then remaining NOCl gas will immediately react with the herbicide to re-create an N-nitroso compound. Excessively long reaction times with concentrated HCl can lead to the formation of other impurities, limiting the utility of this method. Similarly, U.S. Pat. No. 4,185,035 converts nitrosamines utilizing compounds such a PCl.sub.3 or PCl.sub.5.
U.S. Pat. No. 5,405,999 describes a method of removing nitrosamines from a herbicide by contacting the herbicide with an aqueous solution of hydrogen bromide, sulfamic acid, and some form of sulfite. U.S. Pat. No. 4,874,895 also describes a method of removing nitrosamines with an aqueous solution of hydrobromic acid, sulfamic acid, and a bisulfite. The sulfamic acid serves as a scavenger for NOCl. U.S. Pat. No. 5,510,534 describes a method of removing nitrosamines from a herbicide by contacting the herbicide with an aqueous solution containing an oxidant such as alkaline persulfate.
U.S. Pat. No. 4,675,445 describes a method of removing nitrosamines by contacting the composition with an alkyl acyl halide. Similarly, U.S. Pat. No. 4,537,992 describes a method to remove nitrosamines using an acyl halide in combination with an amino-benzoate ester. U.S. Pat. No. 4,970,343 describes a process of removing nitrosamines with hydrobromo salts of an amino benzoate ester.
U.S. Pat. No. 4,127,610 describes a method of removing nitrosamines by treating the herbicide in a liquid phase with a bromine or chlorine molecule. The upper temperature limit is generally 140.degree. C. and preferably 120.degree. C. However, the use of 10 per cent bromine was also reported to cause side reactions such as polymerization. In addition, extended exposure of the dinitroanilines with the denitrosation products under the reaction conditions was reported to result in the formation of further nitrosamines. U.S. Pat. No. 4,134,917 describes a process to remove nitrosamines by reacting them with ketones or aldehydes in the presence of a strong acid.
The above methods use expensive chemicals and/or mineral acids. They require extended reaction times, and generate large quantities of waste products. However, the biggest problem with the majority of these methods is that the reactions are reversible, and unless all of the undesirable products of the denitrosation product are purged from the system, the reverse reaction readily occurs. It is very difficult to get the level of N-nitroso compounds below about 10 ppm using these methods.
The third method of removing nitrosamines is to physically separate them from the remaining herbicide. Several patents relate to the well-known azeotropic distillation of N-nitroso compounds with steam. This method is useful in removing N-nitroso compounds that have a lower molecular weight than the herbicide, and is therefor particularly useful for Trifluralin. U.S. Pat. No. 4,876,388 describes a method of removing nitrosamines from a herbicide by contacting the herbicide with approximately 1 to 4 times the weight of the herbicide with saturated steam at about 105.degree. C. to 110.degree. C. U.S. Pat. No. 4,338,473 describes a method of removing nitrosating agents from a 4-chloro-3,5-dinitrobenzotrifluoride by treating this compound with water at elevated temperatures, with at least partial removal of the water. A portion of the water is distilled off, preferably at a weak vacuum. U.S. Pat. 5,317,004 describes a process to manufacture microencapsulated agriculturally active compounds. The process comprises heating a low-melting material to melting, then combining this with an aqueous solution containing filming agents, homogenizing the two solutions to obtain an emulsion, and then spray drying the emulsion. The inventors discovered that during the microencapsulation step the quantity of nitrosamines in Trifluralin was reduced. For Trifluralin, however, the principal nitrosamine is N-nitroso-di-propylarnine (molecular weight 130, versus 335 for Trifluralin). U.S. Pat. 5,728,881 describes the removal of N-nitroso-di-propylamine from crude Trifluralin by the distillation of volatile components (including water) from the final reaction mixture.
These methods result in large waste streams, and the N-nitroso compounds must still be destroyed. The processing takes as long as several hours. Furthermore, these methods are not useful when the N-nitroso compounds have a molecular weight that is equal to or greater than that of the herbicide. The azeotropic distillation with steam is not effective, therefore, in separating N-nitroso-pendimethalin (molecular weight 310) from Pendimethalin (molecular weight 281). These processes result in a considerable amount of excess material, including nitric oxide scavengers or other treatment chemicals.
What is needed is a method to quickly, economically, and quantitatively eliminate N-nitroso compounds from dinitroaniline herbicides, without adding substantial quantities, i.e., less than 2%, of other inerts to the product. In particular, what is needed is a method of reducing N-nitroso compounds to below the maximum acceptable level in dinitroaniline herbicides, without adding substantial quantities of other inerts to the product. More particularly, what is needed is a method of reducing N-nitroso compounds to below the maximum acceptable level in Pendimethalin, Butralin, and other selected herbicides, without adding substantial quantities of other inerts, reaction products, and the like, to the product.